Percentage grade 4 tumour predicts outcome for prostate adenocarcinoma in needle biopsies from patients with advanced disease: 10-year data from the TROG 03.04 RADAR trial.

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Long-term effects of intermittent androgen suppression therapy on lean and fat mass: a 33-month prospective study.

BACKGROUND: To examine changes to whole body and regional lean mass (LM) and fat mass (FM) over 33 months of intermittent androgen suppression therapy (IAST). METHODS: Phase II cohort study of 72 prostate cancer patients without metastatic bone disease. Patients received flutamide 250 mg tid and leuprolide 22.5 mg three monthly depot for the 9-month initial treatment phase (iTREAT), at which point patients ceased therapy providing PSA <4 ng ml(-1) with continued monitoring for further 2 years (POST). AST was recommenced when PSA exceeded pretreatment level or ≥ 20 ng ml(-1). Body composition was assessed using dual energy X-ray absorptiometry at baseline, completion of treatment phase, and 1 and 2 years post treatment phase (months 21 and 33). RESULTS: LM decreased by 1.3 kg and FM increased by 2.3 kg (P<0.001) following iTREAT. During the POST period, there were no further adverse effects on LM or FM, but also no recovery to pretreatment levels. Patients who failed to recover testosterone by month 33 experienced a significant increase in FM compared with those who recovered eugonadal levels of testosterone (10 nmol ml(-1); P = 0.019). Change in testosterone was moderately correlated to changes in % FM (r = -0.314, P<0.028) and LM (r = 0.300, P<0.036) during POST phase. Waist circumference progressively increased over time and by 2 years, POST had not recovered to baseline levels. CONCLUSIONS: Loss of LM and gain in FM during the 9-month iTREAT was not reversed during 2-year POST, although further deterioration was not observed. Subgroup analysis identified those recovering testosterone showed some body composition improvements. These findings suggest potential benefits of IAST, where testosterone levels are able to recover, to reduce the ongoing adverse effects on body composition, such as the acceleration of sarcopenia and risks associated with metabolic disease.

Comparison of DVH data from multiple radiotherapy treatment planning systems.

This study examined the variation of dose-volume histogram (DVH) data sourced from multiple radiotherapy treatment planning systems (TPSs). Treatment plan exports were obtained from 33 Australian and New Zealand centres during a dosimetry study. Plan information, including DVH data, was exported from the TPS at each centre and reviewed in a digital review system (SWAN). The review system was then used to produce an independent calculation of DVH information for each delineated structure. The relationships between DVHs extracted from each TPS and independently calculated were examined, particularly in terms of the influence of CT scan slice and pixel widths, the resolution of dose calculation grids and the TPS manufacturer. Calculation of total volume and DVH data was consistent between SWAN and each TPS, with the small discrepancies found tending to increase with decreasing structure size. This was significantly influenced by the TPS model used to derive the data. For target structures covered with relatively uniform dose distributions, there was a significant difference between the minimum dose in each TPS-exported DVH and that calculated independently.

Comparison of non-coplanar and coplanar irradiation techniques to treat cancer of the pancreas.

We compared two different techniques of pancreatic irradiation using measures associated with normal tissue complications. Seven consecutive patients with pancreatic cancer were planned for both coplanar and non-coplanar (NCP) external beam radiation treatments, using the same defined anatomical volumes for each patient, in each case. Each pair of plans was then compared using a range of objective criteria. Individual normal tissues were assessed against traditional tolerance limits. Selected dose-points, normal tissue complication probability (NTCP) and equivalent uniform doses (EUD) were also compared, as were indices combining information from individual tissues - total NTCP and total weighted EUD. All individual normal tissues doses were within established tolerance limits. For NCP relative to coplanar planning, NTCP and EUD were lower for all individual tissues in four cases and one case, respectively, i.e. in most cases a benefit to one tissue was offset by detriment to others. Summary measures demonstrated overall benefits for NCP techniques, with the total NTCP in six patients, and with the total weighted EUD in all patients. NCP techniques show potentially useful benefits. We present a new objective measure, the total weighted EUD, which may be particularly useful comparing plans where there are multiple critical tissues.

Adverse effects to quality of life arising from treatment can recover with intermittent androgen suppression in men with prostate cancer.

Health-related quality of life (HQOL) research is a means of broadening the assessment of treatment effects. This longitudinal study investigated the dynamic change to quality of life (QOL) and testosterone dependant physiology in men commencing an intermittent maximal androgen blockade program (IMAB). Two hundred and fifty men were accrued to the multi-centre study of IMAB (Flutamide 250 mg TDS, Leuprolide 22.5 mg depot) ceasing treatment after 9 months if PSA <4 ng/ml, and restarting when PSA >20 ng/ml. QOL was assessed every 3 months for 30 months using the EORTC QLQ-C30 and EORTC QLQ-PR25 module. Data completion for the whole study was 90%. At baseline, our cohort was less symptomatic and had better function than the EORTC reference cohort, which may be related to a shift in clinical practice with time. Testosterone suppression (AS) lead to a significant reduction in global HQOL and deterioration in most function and symptom scales. During the off period, there was a trend of progressive improvement in HQOL that paralleled testosterone recovery but was slower than the rate of deterioration during the treatment phase. Maximum recovery of HQOL occurred most frequently by months 9-12. Testosterone recovery was slower and less complete in older men, and lead to concomitant poorer HOQL recovery. Whilst the magnitude of mean change to scale scores was small, there was a consistent and simultaneous deterioration during maximal androgen blockade (MAB) and improvement during androgen recovery. Older men are more likely to show an impaired testosterone recovery, and this was paralleled by a slower HQOL recovery. Newer methods of analysis to describe results in a way that has meaning to the individual patient are warranted.

A randomised trial of single-dose radiotherapy to prevent procedure tract metastasis by malignant mesothelioma.

A single 9-MeV electron treatment, following invasive thoracic procedures in patients with malignant pleural mesothelioma, was examined. In all, 58 sites were randomised to prophylactic radiotherapy or not. There was no statistically significant difference in tract metastasis. A single 10-Gy treatment with 9-MeV electrons appears ineffective.

A prospective trial of short-fractionation radiotherapy for the palliation of liver metastases.

The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty-eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty-two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high-dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53-66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well-tolerated treatment achieves useful palliation.

A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study.

PURPOSE: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. PATIENTS AND METHODS: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. RESULTS: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms. CONCLUSIONS: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy.

System validation and work practice efficiency gains of a new localization method for stereotactic radiotherapy.

The increased procedural demands of stereotactic localization techniques when compared with conventional treatment practices reduces machine efficiency, an outcome likely to be greatly magnified by the introduction of fractionation to stereotactic techniques. Currently in Australia and New Zealand there are no guidelines for the definition of efficiency. We sought to devise a system to simultaneously validate the accuracy and efficiency of the technique. The frameless relocation methods employed in the Medtronic Sofamor Danek (MSD) stereotactic radiotherapy (SRT) system were studied in the clinical setting. Accuracy has been determined according to the accumulation of errors throughout the planning and treatment process. The clinical demands of the system (staffing and resources) were analysed relative to conventional treatment approaches. Timing studies indicate a mean time of 19.7 min for treatment of a daily SRT fraction (4-5 arcs, single isocentre). Cost and staffing requirements are similar to those for conventional radiotherapy. It is concluded that with the system used, SRT is efficient for routine clinical implementation, with the level of efficiency increasing with increasing patient numbers. It is recommended that a common acceptance standard be developed to allow cross-institutional comparison of the clinical efficiency of new treatment techniques.

Dose perturbation by air cavities in megavoltage photon beams: implications for cavity surface doses.

Gas-filled cavities in the body are known to perturb megavoltage photon beams in radiation therapy. The bowel represents one such cavity where cavity dimensions can vary throughout a treatment course. This has implications for doses to the surface of the bowel. Doses to the first 0.1 mm and 1.0 mm of cavity surfaces were calculated for 6 MV and 18 MV photon beams for a range of cavity sizes. It is found that relatively minor variations in cavity surface doses result over the typical range of rectal cavity size (2-3 cm). However, the variations in surface dose should be considered whenever bowel reactions must be considered, or when the target cells of interest line the bowel itself.

Eligibility audits for the randomized neuropathic bone pain trial (TROG 96.05).

In February 1996 the Trans-Tasman Radiation Oncology Group (TROG) initiated a two-arm, multicentre, prospective randomized trial on radiotherapy for neuropathic pain due to bone metastases (TROG 96.05). This trial compares the response to a single 8-Gy fraction with 20 Gy in five fractions. The accrual target is 270 patients. In order to evaluate compliance with eligibility criteria after approximately 1 year of accrual, an independent audit of the first 42 randomized patients was commissioned. This found that only one of these patients did not have genuine neuropathic pain, but that this patient and seven others (19%) had infringements of other eligibility/exclusion criteria for the trial. Accordingly it was decided to continue the full audit up to 90 patients. This detected no further patients without genuine neuropathic pain, and found only one other eligibility infringement (1/48; 2%). It is concluded that this quality assurance (QA) measure undertaken early in the trial led to significantly improved clinician awareness of, and compliance with, eligibility/exclusion criteria. It also enabled an accurate comparison of outcome data for all randomized versus all eligible patients at the time of the preplanned first interim analysis at 90 patients. In view of the excellent compliance demonstrated in the second audit, a one-in-five sampling is proposed for future audits from centres that have already accrued at least five consecutive eligible patients. This is consistent with TROG QA guidelines now operational.

A role for radiotherapy in neuropathic bone pain: preliminary response rates from a prospective trial (Trans-tasman radiation oncology group, TROG 96.05)

PURPOSE: Radiotherapy (RT) has a proven role in palliation of pain from bone metastases with numerous randomized trials obtaining response rates (RRs) of typically 70-80% regardless of the fractionation employed. However RT for neuropathic bone pain (NBP), i.e., pain with a radiating cutaneous component due to compression/irritation of nerves by tumor has not previously been studied, and its role is thus uncertain. METHODS AND MATERIALS: In February 1996, the Trans-Tasman Radiation Oncology Group (TROG) initiated a multicenter randomized trial comparing a single 8 Gy fraction with 20 Gy in 5 fractions for NBP with an accrual target of 270. Formal interim analyses were planned at 90 and 180 patients. The 90th patient was accrued in June 1998, and data from the first interim analysis with both arms combined form the basis of this report. RESULTS: Forty-four patients were randomized to a single 8 Gy, 46 to 20 Gy in 5 fractions. The commonest primary sites were prostate (34%), lung (28%) and breast (10%). Median age was 68 years (range 37-89). The index site was spine (86%), rib (13%), base of skull (1%). On an intention-to-treat basis, the overall RR was 53/90 = 59% (95% CI = 48-69%), with 27% achieving a complete response and 32% a partial response. The overall RR for eligible patients was 49/81 = 60% (95% CI = 49-71%) with 27% and 33% achieving complete and partial responses respectively. Estimated median time to treatment failure was 3.2 months (95% CI = 2.1-5.1 months), with estimated median survival of 5.1 months (95% CI = 4.2-7.2 months). To date, six spinal cord/cauda equina compressions and four new or progressive pathological fractures have been detected at the index site after randomization, although one cord compression occurred before radiotherapy was planned to commence. In February 1999, the Independent Data Monitoring Committee strongly recommended continuation of the trial. CONCLUSION: Although these results are preliminary, it seems clear that there is indeed a role for RT in the treatment of NBP. Analysis of outcome by treatment arm awaits completion of the randomized trial.

Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?

BACKGROUND AND PURPOSE: The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. PATIENTS AND METHODS: The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. RESULTS: The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. CONCLUSIONS: The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.

Causes for increased myelosuppression with increasing age in patients with oesophageal cancer treated by chemoradiotherapy.

The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesophageal cancer. One or two cycles of cisplatin 80 mg/m2/day followed by 5-fluorouracil 800 mg/m2/day for 4-5 days were administered during the first and fourth or fifth week of radiotherapy using 2 Gy daily fractions. 44 of the patients underwent 5-fluorouracil pharmacokinetic studies. Multiple regression procedures were used to determine the strength of factors that contribute to initial and nadir neutrophil and platelet counts. The kinetics of myeloid response were evaluated from the rates of disappearance and re-appearance of neutrophils and platelets during treatment. Age, fluorouracil dose (or AUC), baseline body weight and neutrophil (or platelet) count were found to be powerfully and independently predictive of both first neutrophil and platelet nadir count. Baseline neutrophil and platelet counts were also found to correlate negatively with advancing age independently of other factors. The rate of descent of both indices, however, was independent of age, baseline count and fluorouracil dose suggesting that variations in the size of the myeloproliferative compartment prior to treatment were responsible for interpatient variations. In addition, the rate of recovery of both indices was not influenced by age amongst patients in whom data was assessable suggesting that proliferation of surviving marrow elements is not compromised by age. These data are compatible with the hypothesis that a progressive depletion of the myeloid stem cell compartment accompanies advancing age, and that this is responsible for increasing myelotoxicity.

Mucosal regeneration during radiotherapy. Trans Tasman Radiation Oncology Group (TROG).

BACKGROUND AND PURPOSE: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. MATERIAL AND METHODS: Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. RESULTS: Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. CONCLUSIONS: This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment.

Factors influencing outcome following radio-chemotherapy for oesophageal cancer. The Trans Tasman Radiation Oncology Group (TROG)

BACKGROUND AND PURPOSES: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. METHODS AND PATIENTS: Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. RESULTS: Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. CONCLUSIONS: Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.

Orchidectomy prior to definitive radiotherapy for localized prostatic cancer.

PURPOSE: To identify potential survival benefits of cytoreductive orchidectomy performed prior to definitive radiation for localized prostate cancer. METHODS AND MATERIALS: Between 1977-1988, all patients with localized prostatic cancer from the Wellington Region received definitive radiotherapy (n = 200). One referring urologist Peter M. Meffen (P.M.M.) had commenced a program of prior orchidectomy followed by definitive radiation treatment (median time to radiation therapy was 5 months, n = 30). RESULTS: Five-year overall survival (OS) and relapse-free survival (RFS) for each stage were Stage A 82%, and 82%; Stage B 75%, and 61%; Stage C 57%, and 38%, respectively. Ten-year OS and RFS for each stage were Stage A 78%, and 72%; Stage B 51%, and 18%; Stage C 32% and 0%, respectively. Multivariate analysis identified prior orchidectomy treatment and histological grade as independently significant prognostic factors for OS and RFS. Factors influencing RFS were clinical stage, prior orchidectomy, and histological grade. Prior orchidectomy was associated with an increase in OS at 5 years when compared to those patients receiving radiotherapy alone, 86% vs. 69%, and maintained at 10 years, 82% vs. 46% (p < 0.05). The two groups were comparable by stage, histological grade, and age. There were no changes in the referral pattern during the study period. CONCLUSIONS: Our results suggest that prior cytoreduction by orchidectomy has a beneficial effect on OS and RFS for patients with localized prostate cancer. It is unclear whether survival benefits are due to the cytoreductive therapy, the adjuvant therapy, or a combination of both. Further study in this area is warranted, ideally in the form of randomized prospective clinical trials.

Heterotopic bone formation affecting the hip joint is preventable in high risk patients by post-operative radiation.

Between 1984 and 1993, 40 high risk patients (45 hips) received postoperative irradiation as prophylaxis against heterotopic ossification (HO). Radiotherapy was commenced within 5 days of the surgery in 43 of 45 hips. The development of HO was assessed by comparison of radiographic films prior to irradiation and at least 2 months after treatment (median interval 12 months). Progression of HO was observed in only two of 45 hips (4.3%) and of clinical significance in one (2.2%). Treatment was well tolerated with no acute complications or loosening of prosthetic components attributable to irradiation. During the study period, the treatment programme changed from 20 Gy in 10 fractions to 6-8 Gy in a single fraction, without loss of treatment efficacy. As well as improving resource utilization, single fraction techniques allow fewer patient transfers thereby reducing patient discomfort and risk of hip dislocation. This procedure is uncomplicated and should be considered more widely in the management of this disabling non-malignant condition.

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.